The recent finding that motility of human blood lymphocytes is a property of T cells and that human serum contains a natural inhibitor to the motile configuration of these lymphocytes has prompted further investigation of the motility of human lymphocytes. The objectives of the proposed research are to (a) purify the serum inhibitor of T lymphocyte motility; (b) characterize the physical and chemical properties of the inhibitor; (c) elucidate the relationship of the inhibitor to B-lipoprotein; (d) define the site of synthesis of the inhibitor as well as its concentration in various tissues; (e) examine the in vivo role of the inhibitor; (f) examine the membrane receptor sites for the inhibitor; (g) investigate whether T and B cell mitogens cause T cells to overcome the effect of the inhibitor; and (h) determine whether lymphocyte motility can be used as a means of examining T cell function in immunologic disorders. The plasma inhibitor will be purified by the sequential use of ultracentrifugation, gel filtration, and agarose electrophoresis. The purified inhibitor will be characterized physico-chemically by standard techniques. The physical relationship of the inhibitor to B-lipoprotein will be investigated by measuring the binding of the purified inhibitor labelled with 125I. The site of synthesis and tissue levels of the inhibitor will be examined by employing an enzyme linked immunosorbent assay for the inhibitor as well as fluorescent conjugates of an antisera to the inhibitor. Relative concentrations will be determined in different tissues and particularly at inflammatory sites. Membrane receptor sites will be probed by using glycosidases, proteases, and lipid specific enzymes. Mitogens will be investigated for their ability to antagonize the effect of the inhibitor upon T cells. The ability of lymphocytes to respond to certain mitogens after initial inhibition with a resumption of the motile configuration and use of the motile configuration as a marker for T cells will be applied to certain immunological diseases. The knowledge from these studies should establish whether lymphocyte motility is an important function of lymphocytes and allow its use as a tool in immunologic disease states.